There is a major international effort to develop renewable alternatives to fossil fuels. One approach is to produce a liquid fuel by enzymatically hydrolyzing carbohydrate polymers in biomass to sugars and fermenting them to ethanol. Cellulose is the main polymer in biomass and cellulases can hydrolyze it to cellobiose, which can be converted to glucose by beta-glucosidase. Extensive research is being carried out to try to obtain cellulases with higher activity on pretreated biomass substrates by screening and sequencing new organisms, engineering cellulases with improved properties and by identifying proteins that can stimulate cellulases. Despite extensive research on cellulases there are major gaps in our understanding of how they hydrolyze crystalline cellulose, act synergistically, and the role of carbohydrate binding modules.